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The primary objective of this thesis was to determine if patients with early onset
(<65 years) non-autosomal dominant AD are more genetically loaded i.e., have more AD
liability genes, than patients with late onset (> 65 years) non-autosomal dominant AD.
Secondary aims were: (i) to examine the effect(s) of the gender of the index case on the
risk of AD to first degree relatives (ii) to examine the effect(s) of the gender of the first
degree relative on their AD risk (iii) to examine the effect(s) of the relationship between the
index case and the first degree relative (parent or sib) on the relative's risk of AD
(iv) to compare the risk estimates for first degree relatives of non-autosomal dominant AD
cases with those for first degree relatives of controls to determine genetic loading, and
(v) if certain subgroups of first degree relatives of AD cases were at an increased risk, to
determine whether this was reflected in the general population. Kaplan-Meier age-specific
risk estimates were calculated for the 2519 first degree relatives of the 453 early and late
onset non-autosomal dominant AD cases seen at the Clinic for Alzheimer Disease and
Related Disorders -UBC Site from 1985 to 1995. Kaplan-Meier risk estimates were also
calculated for 4324 first degree relatives of 796 controls taken from the Canadian Study of
Health and Aging (CSHA). The cumulative lifetime risk estimate to age 88 for first degree
relatives of early onset cases was 7.9± 2.1% compared to 8.0± 1.5% for first degree
relatives of late onset cases, and 4.1 ± 0.6% for first degree relatives of controls. The
difference between the cumulative lifetime risk estimates for first degree relatives of early
and late onset cases was not significant (Z=0.04, p=0.48). The cumulative lifetime risk
estimate for first degree relatives of late onset cases was significantly different from the
cumulative lifetime risk estimate for first degree relatives of controls (Z=2.41, p